The present disclosure generally relates to polymer compositions, methods of forming such polymer compositions, and methods of using such compositions. These compositions and have improved properties that make them useful for a variety of applications; in particular, the loading and delivery of therapeutic agents.
Recognition in nature is a complex orchestration of numerous interactions between individual atoms and cumulative interactions between secondary structures. For example, the active sites of enzymes are composed of several amino acid residues, which noncovalently bind ligand molecules in a very specific manner. However, the activity of the site is dependent on the stabilization of the three-dimensional structure by the interactions of hundreds of other residues within the structure of secondary and tertiary domains.
The term configurational biomimesis refers to the three-dimensional arrangement of chemical groups that can specifically bind a biomolecule via noncovalent forces. This designed recognition involves analyzing the molecular basis of recognition in biological systems and attempts to mimic similar interactions on a molecular level. For example, analysis of biological systems such as enzyme-substrate, receptor-ligand, antibody-antigen, complementary DNA or RNA strands and protein-protein complexes, etc., can yield much information on the type, number, and arrangement of noncovalent chemical forces needed for aqueous recognition.
Configurational biomimesis is, therefore, a subset of molecular imprinting, which produces precise polymer architectures that can selectively recognize molecules and at times, depending on the matrix structure, differentiate with isomeric specificity.
The concept of molecular imprinting manifests itself from two major synergistic effects, (i) shape specific cavities or nanovacuoles that match the template molecule and (ii) chemical groups orientated to form multiple complexation points with the template molecule. In terms of selectivity, the resulting polymer networks are selective due to the particular chemistry of the binding site, the orientation of the chemistry, as well as by the size and shape of the site for the template molecule.
The quality of the receptor mechanism of imprinted polymers can be assessed via a number of parameters. The significant parameters in determining how well a polymeric network can recognize a given molecule are binding affinity (i.e., the equilibrium association or dissociation constant between the ligand molecule and the network), selectivity (i.e., the ability to differentiate between the ligand and other molecules), and the binding capacity (i.e., the maximum ligand bound per mass or volume of polymer). To a lesser extent, binding or imprinting ratios (i.e., the ratio of recognitive network template bound compared to control network) highlights the recognition properties at a specific concentration.
Binding affinity is a measure of how well the template molecule is attracted to the binding site or how well a ligand binds or is held to the receptor macromolecule. Considering equilibrium theory of receptor-ligand interactions, the dissociation constant, Kd, provides a quantitative measure of this level of attraction.